Monoclonal antibody to the human ganglioside GD.sub.2 antigen, and to other melanoma and small cell lung carcinomas are known. For example, U.S. Pat. No. 4,675,287 to Reisfeld et al. discloses a monoclonal antibody to the human ganglioside GD.sub.2 antigen. This antibody is reactive with melanoma and oat cell lung carcinoma cells. This monoclonal antibody is tolerated by the human immune system and thus human immune system does not remove this antibody by immunoactive mechanisms. International Patent Publication WO 8600909 to Reisfeld, R. A. et al is directed to a "Monoclonal antibody directed to human ganglioside GD.sub.2." This patent is the international patent publication related to U.S. Pat. No. 4,675,287 to Reisfeld et al. described above. More specifically, the publication discloses a non-human, mammalian monoclonal receptor produced by a hybridoma formed by fusion of cells from a myeloma cell line and lymphocytes that produce antibodies that react with ganglioside GD.sub.2 from a mammal immunized with a ganglioside GD.sub.2 -containing immunogen is disclosed.
U.S. Pat. No. 4,693,966 to Houghton et al. discloses human monoclonal antibodies from lymphocytes of patients with malignant melanoma. The monoclonal antibodies of Houghton et al. specifically bind to antigens found on surfaces of renal, lung and breast cancer cells. The antibody also detects the cytoplasmic antigen expressed by cells of neuroectodermal origin, such as melanoma cells.
U.S. Pat. No. 4,965,498 to Yamasaki et al. discloses a monoclonal antibody specific to a sugar chain containing an N-glycolylneuramine acid and has the ability to bind to at least N-glycolyl GM.sub.2 ganglioside. Page 1, lines 55-56 acknowledges that monoclonal antibodies against human melanoma which react with glycolipids such as GD.sub.2 ganglioside are known.
U.S. Pat. No. 5,305,559 to Nicolson et al. is directed to methods and compositions for the identification of metastatic human tumors. Monoclonal antibodies of this patent react with human tumor cells and are prepared against a 580 kilodalton glycoprotein antigen gp580. Antibodies are specific for lung metastasis from breast tissue and are not reactive with melanoma tumors.
U.S. Pat. No. 5,091,177 to Hellstrom et al. issued is directed to monoclonal antibodies which define a glycolipid antigen associated with human non-small cell lung carcinomas. Activity with melanoma cells is not disclosed. The monoclonal antibody has an IgG2 isotope.
U.S. Pat. No. 5,134,075 to Hellstrom et al. discloses a monoclonal antibody which binds strongly to a protein antigen associated with human tumors, including lung tumors as well as melanomas and sarcomas. The monoclonal antibody is of the subclass IgG2a.
U.S. Pat. No. 5,240,833 to Nudelman et al. discloses monoclonal antibodies that bind to tumor-associated gangliosides. The monoclonal antibodies have selected preferential reactivity to melanomas, neuroblastomas and adenocarcinomas. They are anti-ganglioside antibodies with specific isotopes such as IgG3 and IgG2a.
U.S. Pat. No. 5,242,824 to Hellstrom et al. discloses novel monoclonal antibodies reactive with a glycolipid cell membrane antigen on the surface of human carcinomas. Monoclonal antibodies react with carcinomas of the lung, ovary and colon. They show no detectable reactivity with melanoma cells.
U.S. Pat. No. 5,270,202 to Raychaudhuri discloses a novel anti-idiotypic antibody IMelpg2 which is specific for melanoma cells. It can be used for the diagnosis and treatment of melanoma tumors.
U.S. Pat. No. 5,208,146 to Irie discloses murine monoclonal anti-idiotype antibodies raised against human monoclonal anti-ganglioside antibody known as L612. The monoclonal antibody is specific for melanoma cells.
U.S. Pat. No. 4,904,596 to Hakomori discloses a hybridoma cell line and monoclonal antibody to fucoganglioside, 6B, which is present in human colonic adenocarcinoma and lung carcinoma cells.
U.S. Pat. No. 5,009,995 to Albino et al. discloses monoclonal antibodies recognized by gp130 antigen of human cells. The monoclonal antibodies are useful in the detection of the gp130 antigen and human cells, including melanoma cells, which contain the antigen.
U.S. Pat. No. 4,918,164 to Hellstrom et al. discloses anti-idiotypic antibodies for immunization against tumor, for inhibition of immune suppression mediated by suppressor T cells or suppressor factors expressing an anti-idiotype against tumors bearing the oncofetal antigen. Monoclonal antibody recognizes a human melanoma associated GD3 ganglioside antigen.
Journal of Immunology, Volume 150, 142A, 1993 discloses an abstract of Chatterjee et al. entitled "Syngeneic Monoclonal Anti-IdiotypeAntibodies Against a Monoclonal Antibody to Human Melanoma-Associated Antigen." The abstract generally discloses that the 1A7 antibody was isolated, but does not disclose a method of obtaining it or provide any of its particular properties or uses.
Patent No. EP 280209 is directed to "Monoclonal antibodies against melanoma-associated antigens, hybridoma cell lines producing these antibodies, and uses of the monoclonal antibodies". This patent to Thurin et al. discloses hybridomas producing antibodies against ganglioside antigens GD.sub.2 and GD.sub.3 which are non-reactive with other ganglioside antigens.
None of the patents nor literature recognize an anti-idiotypic monoclonal antibody specific for melanoma and small cell carcinoma cells which is not tolerated by the human immune system.
Neuroblastomas are highly malignant tumors occurring during infancy and early childhood. Except for Wilms' tumor, they are the most common retroperitoneal tumors in children. Neuroblastomas arise most commonly in the adrenal medulla, but they may also develop in other sympathetic ganglia within the thorax or abdomen. These tumors metastasize early with wide spread involvement of lymph nodes, liver, bone, lung and marrow. The prognosis is often good when the tumor is diagnosed prior to obvious metastasis, but with metastasis, prognosis is poor despite the extensive use of radical surgery, deep X-ray therapy, and chemotherapeutic agents.
Several antigenic determinants have recently been detected on neuroblastoma cells with monoclonal antibodies (Mabs). See Seeger, Ann. Intern. Med., 97, 873 (1982); Wikstrand et al., Cancer Res., 42, 267(1982); Wikstrand et al., J. Neuroimmunlogy, 3, 43 (1982); Eisenbarth et al., Proc. Nat'l Acad. Sci. (USA), 76, 4913 (1979); Liao et al., Eur. J. Immunol., 11, 450 (1981); Seeger et al., Cancer Res., 4, 2714 (1981); Kennett et al., Advances in Neuroblastoma Research, p. 209, Raven Press, New York (Evans ed.) (1980); Seeger et al., J. Immunol., 128, 983 (1982); Kemshead et al., Pediatr. Res., 15, 1282 (1981).
A panel of such antibodies has been reported to be helpful in the differential diagnosis of neuroblastoma and lymphoblastic disorders, Kemshead et al., Pediatr. Res., supra; Kemshead et al., Lancet, 12 (1983). In these same studies, antibodies were used either in immunoperoxidase assays with tumor tissue sections or in direct immunofluorescence assays to detect tumor cells in bone marrow aspirates.
The effective use of Mabs directed to any tumor-associated antigens as diagnostic reagents depends on the quantity, expression and chemical nature of the corresponding antigen. In this regard, Mabs directed to tumor-associated gangliosides have been useful in defining antigens associated with melanoma, neuroblastoma, colon carcinoma, and adenocarcinoma, Hakomori et al., J. Natl. Cancer Inst., 71,231 (1983). One of these antibodies was reported to detect a ganglioside antigen shed into the serum of patients with colon carcinomas, Koprowski et al., Science, 212, 53 (1981). Some of the above neuroblastoma-associated antigens are present in fetal neural tissues whereas others are expressed by both fetal and adult neural tissues. Seeger, Ann. Intern. Med., supra.
Most of the monoclonal antibodies utilized to detect the neuroblastoma-associated antigens are not restricted in their reactivity to neuroectodermal tumors like melanoma and glioma but also recognize common antigens on other malignancies such as a variety of sarcomas and leukemias, Seeger, Ann. Intern. Med., supra. In addition, only some of the antigenic structures on neuroblastoma cells recognized by monoclonal antibodies have been partially characterized by immunochemical means. Thus, a monoclonal antibody designated Mab 390 was reported to react with an antigenic determinant of human Thy-1 that had a molecular weight of 25,000 daltons. Seeger et al., J. Immunol., supra.
Another Mab, designated A2 B5, was reported to recognize a GD2 ganglioside on neurons, Eisenbarth et al., Proc. Nat'l Acad. Sci. (USA), supra. A human monoclonal antibody produced in vitro by a lymphoblast cell line from a melanoma patient was also reported to react with a GD.sub.2 ganglioside present on neuroectoderm-derived tumors, Cahan et al., Proc. Nat'l Acad. Sci. (USA), 79, 7629 (1982).
From a biological point of view, gangliosides are of considerable interest since they have been implicated in a variety of cellular functions, including cell-cell adhesion and communication, as well as cell-substrate interactions, Hakomori et al., J. Nat'l Cancer Inst., supra. Recent studies have emphasized the importance of gangliosides for tumor growth regulation by demonstrating differences in ganglioside composition among cells expressing various degrees of tumorigenicity, Itaya et al., Proc. Nat'l Acad. Sci. (USA), 73, 1568 (1976). Consequently, the use of monoclonal antibodies directed to ganglioside determinants aids in further delineating the role of gangliosides in these processes.
Most of the monoclonal antibodies directed against neuroblastoma-associated antigens that have been reported thus far, Wikstrand et al., Cancer Res., supra; Wikstrand et al., J. Neuro-immunology, supra; Eisenbarth et al., Proc Nat'l Acad. Sci. (USA), supra, recognize a common antigenic determinant on fetal tissues, especially fetal brain, as well as on adult brain and other neural tissues. In addition, cross-reactions of such antibodies have also been reported with normal kidney, fibroblasts, myoblasts, and thymocytes, Seeger et al., Cancer Res., supra, and Seeger et al., J. Immunol., supra, with islet cells, Eisenbarth et al., Proc. Nat'l Acad. Sci. (USA), supra, and with spleen cells, Wikstrand et al., Cancer Res., supra.
Furthermore, some of the monoclonal antibodies reported in the literature are not only restricted in their reactivity to neuroectodermal tumors, such as neuroblastoma, melanoma and glioma, but also show binding to some forms of leukemia, osteogenic sarcoma, rhabdomyosarcoma, leiomyosarcoma and even to carcinomas of the lung and breast, Seeger, Ann. Intern. Med., supra.
A monospecific human monoclonal antibody, (anti-OFA I-2), produced in vitro by a lymphoblast cell line that originated from a melanoma patient was reported to detect a GD2 ganglioside on human melanoma, glioma and neuroblastoma cells, while reportedly not reacting with a variety of cell lines derived from carcinomas and from different lymphoid tumors, Cahan et al., Proc. Nat'l Acad. Sci. (USA), supra, and Irie et al., Proc. Nat'l Acad. Sci. (USA), 79, 5666 (1982). However, problems have arisen when such a human monoclonal antibody is used for immunoperoxidase assays of human tissues in that the anti-human secondary antibody required for such assays causes a large amount of non-specific background reactivity.
Heterogeneity of neuroblastomas with regard to cell surface antigenic expression has been reported in Seeger, Ann. Intern. Med., supra; Kemshead et al., Pediatr. Res., supra; Kemshead et al., Int. J. Cancer, 27, 447(1981); and, Kemshead et al., Proc. Am. Assoc. Cancer Res., 2, 399 (1981). As discussed in these publications, Mab A2 B5 failed to react with some human neuroblastoma lines tested, and quantitative differences in antigenic expression were observed between different cell cultures. Analysis of tumor cells in heavily infiltrated bone marrow aspirates indicated that only 70 percent of the samples reacted with A2 B5, suggesting that the heterogeneity seen in the expression of antigen on cell lines is paralleled in fresh tumor material, Kemshead et al., Int. J. Cancer, supra.
Thus there is a need in the art for new methods of detecting and treating melanoma and small cell carcinoma. The present invention overcomes the deficiencies of the prior art by providing an anti-idiotypic antibody 1A7 raised against anti-GD2mAb 14G2a, which is not tolerated by the human immune system, and thus may be used as a vaccine to stimulate the immune system. This property of the present monoclonal antibody makes it ideal for a new immuno-therapeutic approach to cancer.